Surgical Management of Movement Disorders potx

Surgical Management of Movement Disorders edited by Gordon H.. We intended this book to be a thorough review of the surgical ments currently available for various movement disorders, wit

Surgical Management

of Movement Disorders

NEUROLOGICAL DISEASE AND THERAPY

Advisory Board

Louis R Caplan, M.D.

Professor of NeurologyHarvard University School of MedicineBeth Israel Deaconess Medical CenterBoston, Massachusetts

St Louis, Missouri

Bruce Ransom, M.D., Ph.D.

Warren Magnuson ProfessorChair, Department of NeurologyUniversity of Washington School of Medicine

Seattle, Washington

Kapil Sethi, M.D.

Professor of NeurologyDirector, Movement Disorders ProgramMedical College of GeorgiaAugusta, Georgia

Mark Tuszynski, M.D., Ph.D.

Associate Professor of NeurosciencesDirector, Center for Neural RepairUniversity of California–San Diego

La Jolla, California

1 Handbook of Parkinson’s Disease, edited by William C Koller

2 Medical Therapy of Acute Stroke, edited by Mark Fisher

3 Familial Alzheimer’s Disease: Molecular Genetics and Clinical Perspectives, edited by Gary D Miner, Ralph W Richter, John P Blass, Jimmie L Valentine, and Linda A Winters-Miner

4 Alzheimer’s Disease: Treatment and Long-TermManagement, edited by Jeffrey L Cummings and Bruce L Miller

5 Therapy of Parkinson’s Disease, edited by William C Koller and George Paulson

6 Handbook of Sleep Disorders, edited by Michael J Thorpy

7 Epilepsy and Sudden Death, edited by Claire M Lathersand Paul L Schraeder

8 Handbook of Multiple Sclerosis, edited by Stuart D Cook

9 Memory Disorders: Research and Clinical Practice, edited by Takehiko Yanagihara and Ronald C Petersen

10 The Medical Treatment of Epilepsy, edited by Stanley R Resor, Jr., and Henn Kutt

11 Cognitive Disorders: Pathophysiology and Treatment, edited by Leon J Thal, Walter H Moos,

and Elkan R Gamzu

12 Handbook of Amyotrophic Lateral Sclerosis, edited byRichard Alan Smith

13 Handbook of Parkinson’s Disease: Second Edition, Revisedand Expanded, edited by William C Koller

14 Handbook of Pediatric Epilepsy, edited by Jerome V Murphy and Fereydoun Dehkharghani

15 Handbook of Tourette’s Syndrome and Related Tic and Behavioral Disorders, edited by Roger Kurlan

16 Handbook of Cerebellar Diseases, edited by Richard Lechtenberg

17 Handbook of Cerebrovascular Diseases, edited by Harold P Adams, Jr

18 Parkinsonian Syndromes, edited by Matthew B Stern and William C Koller

19 Handbook of Head and Spine Trauma, edited by Jonathan Greenberg

20 Brain Tumors: A Comprehensive Text, edited by Robert A Morantz and John W Walsh

21 Monoamine Oxidase Inhibitors in Neurological Diseases,edited by Abraham Lieberman, C Warren Olanow,Moussa B H Youdim, and Keith Tipton

22 Handbook of Dementing Illnesses, edited by John C Morris

23 Handbook of Myasthenia Gravis and MyasthenicSyndromes, edited by Robert P Lisak

24 Handbook of Neurorehabilitation, edited by David C Good and James R Couch, Jr

25 Therapy with Botulinum Toxin, edited by Joseph Jankovicand Mark Hallett

26 Principles of Neurotoxicology, edited by Louis W Chang

27 Handbook of Neurovirology, edited by Robert R McKendall and William G Stroop

28 Handbook of Neuro-Urology, edited by David N Rushton

29 Handbook of Neuroepidemiology, edited by Philip B Gorelick and Milton Alter

30 Handbook of Tremor Disorders, edited by Leslie J Findleyand William C Koller

31 Neuro-Ophthalmological Disorders: Diagnostic Work-Upand Management, edited by Ronald J Tusa

and Steven A Newman

32 Handbook of Olfaction and Gustation, edited by Richard L Doty

33 Handbook of Neurological Speech and LanguageDisorders, edited by Howard S Kirshner

34 Therapy of Parkinson’s Disease: Second Edition, Revised and Expanded, edited by William C Koller and George Paulson

35 Evaluation and Management of Gait Disorders, edited by Barney S Spivack

36 Handbook of Neurotoxicology, edited by Louis W Changand Robert S Dyer

37 Neurological Complications of Cancer, edited by Ronald G Wiley

38 Handbook of Autonomic Nervous System Dysfunction,edited by Amos D Korczyn

39 Handbook of Dystonia, edited by Joseph King Ching Tsuiand Donald B Calne

40 Etiology of Parkinson’s Disease, edited by Jonas H Ellenberg, William C Koller, and J William Langston

41 Practical Neurology of the Elderly, edited by Jacob I Sageand Margery H Mark

42 Handbook of Muscle Disease, edited by Russell J M Lane

43 Handbook of Multiple Sclerosis: Second Edition, Revised and Expanded, edited by Stuart D Cook

44 Central Nervous System Infectious Diseases and Therapy,edited by Karen L Roos

45 Subarachnoid Hemorrhage: Clinical Management, edited by Takehiko Yanagihara, David G Piepgras, and John L D Atkinson

46 Neurology Practice Guidelines, edited by Richard Lechtenberg and Henry S Schutta

47 Spinal Cord Diseases: Diagnosis and Treatment, edited byGordon L Engler, Jonathan Cole, and W Louis Merton

48 Management of Acute Stroke, edited by Ashfaq Shuaiband Larry B Goldstein

49 Sleep Disorders and Neurological Disease, edited byAntonio Culebras

50 Handbook of Ataxia Disorders, edited by Thomas Klockgether

51 The Autonomic Nervous System in Health and Disease,David S Goldstein

52 Axonal Regeneration in the Central Nervous System, edited by Nicholas A Ingoglia and Marion Murray

53 Handbook of Multiple Sclerosis: Third Edition,edited by Stuart D Cook

54 Long-Term Effects of Stroke, edited by Julien Bogousslavsky

55 Handbook of the Autonomic Nervous System in Healthand Disease, edited by C Liana Bolis, Julio Licinio, and Stefano Govoni

56 Dopamine Receptors and Transporters: Function, Imaging, and Clinical Implication, Second Edition, edited by Anita Sidhu, Marc Laruelle, and Philippe Vernier

57 Handbook of Olfaction and Gustation: Second Edition,Revised and Expanded, edited by Richard L Doty

58 Handbook of Stereotactic and Functional Neurosurgery,edited by Michael Schulder

59 Handbook of Parkinson’s Disease: Third Edition, edited byRajesh Pahwa, Kelly E Lyons, and William C Koller

60 Clinical Neurovirology, edited by Avindra Nath and Joseph R Berger

61 Neuromuscular Junction Disorders: Diagnosis andTreatment, Matthew N Meriggioli, James F Howard, Jr.,and C Michel Harper

62 Drug-Induced Movement Disorders, edited by Kapil D Sethi

63 Therapy of Parkinson’s Disease: Third Edition, Revised andExpanded, edited by Rajesh Pahwa, Kelly E Lyons, andWilliam C Koller

64 Epilepsy: Scientific Foundations of Clinical Practice, edited by Jong M Rho, Raman Sankar,

and José E Cavazos

65 Handbook of Tourette’s Syndrome and Related Tic and Behavioral Disorders: Second Edition, edited by Roger Kurlan

66 Handbook of Cerebrovascular Diseases: Second Edition,Revised and Expanded, edited by Harold P Adams, Jr

67 Emerging Neurological Infections, edited by Christopher Power and Richard T Johnson

68 Treatment of Pediatric Neurologic Disorders,Harvey S Singer, Eric H Kossoff, Adam L Hartman,and Thomas O Crawford

69 Synaptic Plasticity: Basic Mechanisms to ClinicalApplications, edited by Michel Baudry, Xiaoning Bi, and Steven S Schreiber

70 Handbook of Essential Tremor and Other TremorDisorders, edited by Kelly E Lyons and Rajesh Pahwa

71 Handbook of Peripheral Neuropathy, edited by Mark B Bromberg and A Gordon Smith

72 Carotid Artery Stenosis: Current and Emerging Treatments,edited by Seemant Chaturvedi and Peter M Rothwell

73 Gait Disorders: Evaluation and Management, edited byJeffrey M Hausdorff and Neil B Alexander

74 Surgical Management of Movement Disorders,edited byGordon H Baltuch and Matthew B Stern

Surgical Management

of Movement Disorders

edited by

Gordon H Baltuch

University of Pennsylvania Philadelphia, Pennsylvania, U.S.A.

Matthew B Stern

University of Pennsylvania Philadelphia, Pennsylvania, U.S.A.

Boca Raton London New York Singapore

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Movement disorders represent major causes of neurological disability andeventual mortality affecting millions of people across the globe FromParkinson’s disease to spasticity, these neurological disorders devastateyoung and old worldwide While progress continues to be made towardeffective treatment, many limitations remain.

The combination of the limitation of medical therapy and surgicaltechnological advances have, however, led to an exponential growth in func-tional neurosurgery in the last 5 years Surgery represents an alternativewhere there existed only finite treatment options before This field is devel-oping rapidly with emerging novel therapies as well as evolving indicationsfor existing procedures

We intended this book to be a thorough review of the surgical ments currently available for various movement disorders, with an emphasis

treat-on surgical indicatitreat-ons and results of surgery It should be of utmost interest

to practitioners and trainees in the clinical neurosciences surgery) who want a better understanding of candidates for movement dis-order surgery, the current surgical procedures, the effected results of surgery,and the complication rate of these procedures Our goal was to summarizethe current status of the field as well as make projections for the next fewyears

(neurology/neuro-Gordon H BaltuchMatthew B Stern

v

Preface v

Contributors xiii

1 Overview 1 Kelvin L Chou, Gordon H Baltuch, and Matthew B Stern

1 Introduction 1

2 Pathophysiology of Movement Disorders 2

3 Surgical Treatment of Movement Disorders 5

4 Conclusions 16

References 16

SECTION I: PARKINSON’S DISEASE

2 Patient Selection and Indications for Surgery 27 Jill L Ostrem, Philip A Starr, and William J Marks, Jr.

1 Introduction 27

2 Importance of Patient Selection 28

3 Indications for Surgery 28

4 Ablative Procedures vs Deep Brain Stimulation 35

5 Unilateral vs Bilateral Treatment 36

6 Previous Surgery for Parkinson’s Disease 37

3 Surgical Technique and Complication Avoidance 45 Joshua M Rosenow and Ali R Rezai

6 Mapping the STN: Confirming the Optimal Target 53

7 Securing the Electrode 55

5 Novel Surgical Strategies: Motor Cortex Stimulation,

Transplantation, Gene Therapy, Stem Cells, and

CNS Drug Delivery 83 Jason M Schwalb and Andres M Lozano

1 Introduction 83

2 Limitations of Current Therapy 83

3 Motor Cortex Stimulation 84

4 History of Transplantation 85

5 Ethics of Sham Surgery 89

6 Future Directions in Implanting Dopaminergic

Neurons 90

7 Induction of Endogenous Stem Cells 92

8 Trophic Factors Rather than Dopaminergic Neurons— GDNF Therapy 92

9 Gene Therapy for Parkinson’s Disease 93

10 Genetic Manipulation of Stem Cells 96

11 Conclusions 96

12 Additional Resources 97

References 97

SECTION II: ESSENTIAL TREMOR

6 Essential Tremor: Patient Selection, Technique,

and Surgical Results 111 Eun-Kyung Won, Habib E Ellamushi, Uzma Samadani, and Gordon H Baltuch

1 Introduction 111

2 Clinical Characteristics and Epidemiology 111

3 Genetics and Etiology 113

4 Pathophysiology 113

5 Pharmacological Treatment for Essential Tremor 115

6 Surgical Therapy for ET 116

SECTION IV: DYSTONIA

8 Dystonia: Classification, Etiology, and Therapeutic

Options 135 Galit Kleiner-Fisman and Santiago Figuereo

1 Introduction 135

2 Classification 136

3 Etiology and Pathophysiology 139

4 Best Medical Therapy 142

5 Surgical Therapy 148

6 Anatomical Targets in DBS Surgery 149

7 Surgical Technique 153

8 Results of Surgery in Dystonia 154

9 Conclusions 157

References 157

SECTION V: CERVICAL DYSTONIA

9 Chemodenervation: Botulinum Toxin 169 Tanya Simuni

2 Pathophysiology of Tourette’s Syndrome 216

3 Conservative Treatment of Tourette’s Syndrome 217

4 Ablative Surgical Treatment for Tourette’s

Syndrome 217

5 Deep Brain Stimulation for Tourette’s Syndrome 220

6 Conclusions 221

References 221

SECTION VI: HEMIFACIAL SPASM

13 Botulinum Toxin/Microvascular Decompression—Indication, Technique, and Surgical Results 227 Fre´de´ric Schils, Nicolas de Tribolet, and Michel R Magistris

1 Introduction 227

2 Epidemiology 228

3 Symptoms and Clinical Signs 229

4 Diagnosis, Staging, Classification 229

1 Introduction 257

Gordon H Baltuch Department of Neurosurgery, Penn NeurologicalInstitute, University of Pennsylvania School of Medicine, Philadelphia,Pennsylvania, U.S.A.

Kelvin L Chou Department of Clinical Neurosciences, Brown

University Medical School, Providence, Rhode Island, U.S.A

Nicolas de Tribolet Department of Neurosurgery, University of Geneva,Geneva, Switzerland

Habib E Ellamushi The Royal Hospital of St Bartholomew and TheRoyal London Hospital, London, U.K

Jean-Pierre Farmer Division of Pediatric Neurosurgery, McGill

University Health Centre, Montreal, Quebec, Canada

Santiago Figuereo Department of Neurosurgery, Philadelphia VeteransAdministration Hospital, University of Pennsylvania, Philadelphia,Pennsylvania, U.S.A

Joseph Ghika Neurology Service, Centre Hospitalier UniversitaireVaudois, Lausanne, Switzerland

Jeff D Golan Division of Neurosurgery, McGill University, Montreal,Quebec, Canada

Line Jacques Division of Neurosurgery, McGill University, Montreal,Quebec, Canada

xiii

Galit Kleiner-Fisman Parkinson’s Disease Research Education andClinical Center (PADRECC), Philadelphia Veterans AdministrationHospital, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.Andres M Lozano Division of Neurosurgery, Toronto Western

Hospital, University of Toronto and University Health Network,

Toronto, Ontario, Canada

Michel R Magistris Department of Neurology, University of Geneva,Geneva, Switzerland

William J Marks, Jr Department of Neurology, University of

California, San Francisco and San Francisco Veterans Affairs MedicalCenter, San Francisco, California, U.S.A

Sandeep Mittal Division of Pediatric Neurosurgery, McGill UniversityHealth Centre, Montreal, Quebec, Canada

Jill L Ostrem Department of Neurology, University of California,San Francisco and San Francisco Veterans Affairs Medical Center,San Francisco, California, U.S.A

Ali R Rezai Department of Neurosurgery, Cleveland Clinic LernerCollege of Medicine, Cleveland, Ohio, U.S.A

Joshua M Rosenow Department of Neurosurgery, Feinberg School ofMedicine of Northwestern University, Chicago, Illinois, U.S.A

Uzma Samadani Department of Neurosurgery, University of

Pennsylvania, Philadelphia, Pennsylvania, U.S.A

Fre´de´ric Schils Department of Neurosurgery, University of Geneva,Geneva, Switzerland

Jason M Schwalb Division of Neurosurgery, Toronto Western

Hospital, University of Toronto and University Health Network,

Toronto, Ontario, Canada

Tanya Simuni Department of Neurology, Feinberg School of Medicine,Northwestern University, Chicago, Illinois, U.S.A

Philip A Starr Department of Neurosurgery, University of California,San Francisco and San Francisco Veterans Affairs Medical Center,San Francisco, California, U.S.A

Matthew B Stern Parkinson’s Disease and Movement Disorders

Center, Pennsylvania Hospital, University of Pennsylvania School ofMedicine, Philadelphia, Pennsylvania, U.S.A

Atsushi Umemura Department of Neurosurgery, Nagoya City

University Medical School, Mizuho-ku, Nagoya, Japan

Jean-Guy Villemure Neurosurgery Service, Centre Hospitalier

Universitaire Vaudois, Lausanne, Switzerland

Franc¸ois Vingerhoets Neurology Service, Centre Hospitalier

Universitaire Vaudois, Lausanne, Switzerland

Eun-Kyung Won Department of Neurosurgery, University of

Minnesota, Minneapolis, Minnesota, U.S.A

Kelvin L Chou

Department of Clinical Neurosciences, Brown University Medical School,

Providence, Rhode Island, U.S.A

Surgery for the field of movement disorders has evolved significantlysince Spiegel et al first described stereotaxis in 1947 (1) Much of this progresshas been made within the last decade with the development of techniquesfor precise targeting of brain structures and the discovery of new targetsand indications for existing procedures such as deep brain stimulation(DBS) This chapter provides a general overview of the field of movement

1

disorders surgery, including a brief summary of basal ganglia structure andfunction, as well as discussions of the major surgical treatments available for

PD, essential tremor (ET), other tremor disorders, dystonia, and spasticity

2 PATHOPHYSIOLOGY OF MOVEMENT DISORDERS

All movement disorders are believed to result from abnormalities of the basalganglia Our understanding of the organization and function of the basal gang-lia has grown significantly in the modern era, largely as a result of recentexperience with stereotactic neurosurgery in humans and animal models.Although current theories do not adequately account for the clinical findingsseen with all disorders of involuntary movement, it is still essential for thoseinterested in functional neurosurgical procedures to be familiar with the basicanatomy and functional organization of the basal ganglia

2.1 Structure and Function of the Basal Ganglia

A detailed discussion of basal ganglia anatomy and function is beyond thescope of this chapter, but a brief summary follows The basal ganglia areorganized into several parallel circuits (associative, limbic, motor, andoculomotor) that connect cortical regions with thalamic and basal ganglianuclei (2) Disturbances of the motor circuit are believed to manifest

as movement disorders In the classical model of basal ganglia function, abalance between two opposing pathways in the motor circuit, the directand indirect pathways, regulates normal voluntary movement (3) Both path-ways begin with neurons in cortical motor areas projecting to the putamen,which in turn sends signals that ultimately terminate in the internal segment

of the globus pallidus (GPi) Putamenal output in the indirect pathway,however, travels through the external segment of the globus pallidus (GPe)and subthalamic nucleus (STN) before it reaches the GPi, whereas the directpathway projects directly from the putamen to the GPi The majority ofGPi output is directed toward the thalamus, which sends projections to thesupplementary motor area, the premotor cortical area, and the primarymotor cortex Activation of the direct pathway decreases the normal inhi-bitory outflow from the GPi to the thalamus, leading to increased corticalmotor activation and the facilitation of voluntary movement In contrast,stimulation of the indirect pathway causes inhibition of the GPe, disinhibition

of STN excitatory fibers, and an increase in the inhibitory outflow from theGPi onto the thalamus, resulting in decreased output to the motor cortexand suppression of voluntary movement

The exact mechanism by which the basal ganglia interpret theinformation flowing through these two opposing motor circuit pathways

to control normal movement is unclear Two theories have been proposed:scaling and focusing (2–4) In the scaling hypothesis, movement is controlled

by temporally changing activity in the basal ganglia For example, putamenaloutput would first facilitate a particular movement by disinhibiting the thala-mus through the direct pathway, and subsequently stop the ongoing movement

by causing the same GPi neurons to increase inhibition of the thalamusthrough the indirect pathway In the focusing hypothesis, movement is allowed

to proceed by stimulation of the direct pathway, whereas extra, unnecessarymovements are suppressed by activity in the indirect pathway Unfortunately,both models are likely oversimplifications of the true underlying mechanism,since they do not account for all experimental findings

2.2 Pathophysiologic Models of Hypo- and Hyperkinetic

Movement Disorders

Based on the model of basal ganglia function described above, an imbalancebetween the direct and indirect pathways accounts for the clinical manifes-tations of hypo- and hyperkinetic disorders The release of dopamine fromnerve terminals in the striatum appears to stimulate the direct pathwayand inhibit the indirect pathway, thus effectively facilitating movement (5).Consequently, degeneration of the dopaminergic nigrostriatal pathway, asseen in parkinsonism, would result in decreased dopamine receptor activa-tion and disinhibition of the indirect pathway, leading to increased activity

in the STN and GPi The increased inhibitory outflow from GPi on thethalamus would decrease cortical motor activation, with the end result beingslowed movements, or bradykinesia Conversely, hyperkinetic disorders such

as Huntington’s disease (HD) are thought to result from excess dopamine,causing overactivity of the direct pathway, less inhibitory activity fromGPi on the thalamus, increased activity of the thalamocortical projections,and excessive involuntary movement

2.2.1 Hypokinetic Movement Disorders

There is considerable evidence supporting the classical model for the nian state For example, in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated monkeys, neuronal firing frequency is increased in the STNand GPi and reduced in the GPe, consistent with the predictions of the abovemodel (6,7) Further support comes from advanced PD patients treated withSTN and GPi DBS, where stimulation clearly improves parkinsonian symp-toms (8–11) and increases activity in cortical motor areas as detected bypositron emission tomography (PET) imaging (12)

parkinso-There are many inconsistencies with this model, however For instance, alesion in the thalamus should worsen PD motor symptoms due to decreasedactivity of the thalamocortical projections, yet, thalamic lesioning and thalamicDBS have both been proven to suppress parkinsonian tremor (13,14) In addi-tion, pallidotomy should result in excessive movement (i.e., dyskinesias)

because of decreased inhibition on the thalamus, but in fact, the opposite istrue (15).

This has led to a rethinking of the classical model, with some gators proposing that it is the overall pattern of basal ganglia activity that isaltered in PD, rather than the rate of activity of individual structures (16).Studies have suggested that in the normal brain, information flows throughindependent and parallel circuits within the basal ganglia, while in the par-kinsonian brain, these circuits break down, and interconnections betweenthese circuits become active and synchronized (17) This synchronization

investi-is believed to contribute to the parkinsonian state Lesions of the STNand GPi may change this pattern back to a more ‘‘normal’’ pattern ofneuronal transmission through the basal ganglia Indirect evidence for thiscomes from human PET imaging studies that have shown a restoration ofnormal cortical activity after lesions of the STN or GPi (12,18)

2.2.2 Hyperkinetic Movement Disorders

As explained above, the classical model predicts that hyperkinetic ment disorders result from a reduction in GPi activity and an increase inthalamic and cortical activity In fact, it has been shown that MPTP-treatedmonkeys given levodopa or apomorphine have a gradual reduction in GPifiring rate as the monkeys transition from an ‘‘off’’ state, to an ‘‘on’’ statewithout dyskinesias, to an ‘‘on’’ state with dyskinesias, supporting thismodel (19) GPi discharge rates are also reduced in other hyperkinetic dis-orders, such as dystonia and hemiballismus (16) However, decreased GPiactivity cannot account for hyperkinetic movements by itself; otherwise,lesions of the globus pallidus would be expected to result in extra move-ments As with the parkinsonian model, many experts now think that it

move-is the pattern of GPi activity, rather than the rate of GPi activity, that move-isimportant in determining movement (16,20) It may be that the absence ofactivity is preferable to abnormal activity, which is why surgical lesioningimproves clinical symptoms

The pathophysiology of tremor, whether in PD, ET, or cerebellartremor, is even less clear, and remains hotly debated There may be someperipheral afferent component to the development of tremor, but it is morelikely that a central mechanism is responsible Evidence for this includesrecordings of neuronal rhythmic activity in the thalamus that are synchro-nized with tremor activity in the limb in patients with ET and cerebellartremor (21), and recordings of rhythmic activity in the STN that correlatewith contralateral tremor in PD patients (22,23) Other supporting evidenceincludes the fact that thalamic stimulation improves tremor, whether for PD

or ET (13) Whatever the true mechanism, however, it is clear that muchwork remains to be completed before we can fully comprehend the complexmechanisms underlying abnormal movements

3 SURGICAL TREATMENT OF MOVEMENT DISORDERS

3.1 Parkinson’s Disease

PD is a slowly progressive neurodegenerative disorder characterized by

a clinical triad of motor features—tremor, bradykinesia, and rigidity Idealcandidates for surgery should have a clear response to levodopa therapy,but continue to have severe motor fluctuations, dyskinesias, or intractabletremor despite optimal medical therapy Older patients tend to fare worseafter surgery, as do patients with cognitive impairment, so comprehensiveneuropsychological testing should be performed prior to surgery (10,24)

It is also being increasingly recognized that psychiatric symptoms such

as depression worsen after DBS procedures (25), so more centers are porating a psychiatric screen into the DBS evaluation process Patients withatypical parkinsonism, such as progressive supranuclear palsy and multiplesystem atrophy, are not candidates for surgery (26,27)

incor-3.1.1 Ablative Procedures

Prior to the discovery of levodopa, thalamotomies were performed routinelyfor PD However, they were only effective for tremor, and bilateral proce-dures resulted in a high incidence of dysarthria and cognitive side effects(28,29) Given the excellent results from pallidotomy in PD and the develop-ment of DBS, which holds the advantage of reversibility and fewer sideeffects with bilateral procedures, thalamotomies are no longer recommendedfor treatment of PD

Laitinen et al (30) revived the posteroventral pallidotomy for thetreatment of PD in 1992 Of 38 patients followed for a mean of 28 months,92% had ‘‘complete relief or almost complete relief’’ of bradykinesia and rigid-ity, and that 81% had ‘‘complete relief or almost complete relief’’ of tremor.While many authors have reported similar results from this procedure withshort-term follow-up (15,31–34), other investigators, in contrast to Laitinen

et al (30), have reported a decline in surgical benefit from pallidotomy withlong-term follow-up (35–37) Although these studies have consistently shownthat pallidotomy’s effects on tremor and dyskinesias are maintained at 3–5years, other measures, such as the total off-period motor score, the ipsilateralmotor score, the contralateral bradykinesia subscore, and the activities of dailyliving subscore, deteriorate with time However, it should be noted that all ofthese studies have followed unilateral pallidotomy patients only, largelybecause of reports of unacceptable speech and neuro behavioral side effectsfrom bilateral pallidotomy (38–41) As the natural history of PD suggests thatthe disease will eventually spread bilaterally, it is not surprising that the benefit

of unilateral pallidotomy diminishes with time

With regards to subthalamotomy, although animal studies hadrepeatedly shown that parkinsonian signs improved with ablative lesions ofthe STN, very few surgeons attempted to lesion the STN in humans for fear

of causing hemiballismus (42) However, most clinical reports have shownthat hemiballismus in subthalamotomy patients does not occur as often aspreviously thought (43–46) Unilateral subthalamotomy in patients withadvanced PD has been demonstrated to decrease the Unified Parkinson’sDisease Rating Scale (UPDRS) off-medication motor scores by about 30–50%(44–46) Persistent, lesion-induced dyskinesias have been problematic for only

a few patients overall, with two requiring additional surgical procedures tocontrol the choreic movements and another dying from aspiration pneumonia.The results of bilateral subthalamotomy have been reported for only two PDpatients in the literature (43) Both patients showed an impressive reduction inUPDRS motor scores, with one patient going from 50 to 16, and the secondimproving from 64 to 16, without adverse effects

3.1.2 Deep Brain Stimulation

Stimulation of the thalamic ventralis intermedius (VIM) nucleus for sonian or other tremor of the limbs was the first Food and Drug Administration(FDA) approved indication for DBS, heralding a new era in functional neuro-surgery Thalamic DBS, in multiple long-term studies, has been shown to be safeand effective for parkinsonian tremor (47–49) Unfortunately, as with thala-motomy, other parkinsonian symptoms are unimproved and prevent thisprocedure from being useful in the long-term treatment of PD

parkin-With reports of pallidotomy being effective for all the motor features

of PD, and the gaining acceptance of thalamic stimulation for tremor, manysurgical centers tried to see if stimulation of the GPi could help the parkin-sonian symptoms not addressed by VIM stimulation, and the results havebeen positive In one of the largest prospective double blind studies pub-lished, 38 PD patients underwent implantation of DBS electrodes bilaterally

in the GPi (11) Stimulation produced a 37% median improvement in the offmedication UPDRS score at 6 months Furthermore, the amount of ‘‘on’’time during the day without dyskinesias increased from 28% to 64%, whileamount of ‘‘off’’ time decreased from 37% to 24% The dyskinesia scoreimproved by about 66% Unfortunately, the mean daily levodopa dosewas not significantly changed

An increasing number of long-term studies evaluating GPi stimulation

in patients with PD have been published in recent years, but it appears that thebenefits seen early on may not endure Visser-Vandewalle et al (50) followed

26 patients with unilateral GPi electrodes for a mean of 32.7 months, andfound that while GPi stimulation was beneficial at 3 months for symptomsboth contralaterally and ipsilaterally, it was unsatisfactory at long-termfollow-up, leading the authors to conclude that unilateral pallidal stimulationwas not an effective treatment for advanced PD Ghika et al (51) followed six

PD patients treated with bilateral pallidal stimulation for 2 years, and whilethere were still significant improvements in the UPDRS motor score and

in the amount of ‘‘on’’ time at 2 years compared to baseline, a slight

worsening after 1 year was observed In the six patients with bilateral GPielectrodes for PD followed for a mean of 3 years by Durif et al (52), theamount of time spent in the ‘‘off’’ state returned to the preoperative valueafter 2 years, even though improvements in UPDRS motor scores andseverity of dyskinesias were sustained Finally, Volkmann et al (53) followed

11 patients treated with chronic bilateral pallidal stimulation for up to 5 years.Although there was a sustained reduction in dyskinesias at 5 years, UPDRSmotor scores declined over time, despite continued levodopa responsivenessand changes in electrical stimulation parameters Overall, the levodopa doseremained unchanged after surgery, but had to be increased in some patients

In all of these studies, complications were generally transient, and could berelieved by adjusting the stimulator The hypophonia, dysarthria, and neuro-behavioral disturbances commonly reported with bilateral pallidotomy(38,40,41) were not seen with bilateral GPi stimulation

In contrast, the benefits of DBS for PD appear to be longer lastingwith STN stimulation, a technique that was pioneered by Benabid and hiscolleagues in the mid-1990s (54,55) Initial studies of subthalamic stimula-tion in patients with advanced PD demonstrated a reduction in the UPDRSmotor score by 40–60%, as well as a decrease in dyskinesias and the dailylevodopa dose by about 50% (8,10,11) STN DBS also decreased the amount

of time in the off medication state, and other studies showed improvement

in gait and balance (56), and even off-period dystonia (55) In the longestlong-term follow-up study of STN stimulation in PD to date, Krack et al.reported that the UPDRS motor scores at 5 years while off medication were54% better than preoperative scores (57) Furthermore, average dailylevodopa dose and severity of dyskinesias continued to be significantlydecreased compared to baseline Unfortunately, speech, postural stability,and freezing continued to progress, which the authors concluded wasconsistent with the natural history of PD Two other groups found similarresults at 2 years (58,59), although the Toronto group (59) noticed thatUPDRS axial subscores, as well as the UPDRS motor score, had diminished

at the most recent follow-up For all of these studies, most adverse eventsappeared to be transient; however, persistent events included cognitivedecline, and mood changes such as depression and anxiety One patient inthe study by Krack et al (57) committed suicide

3.1.3 Comparison of Targets and Procedures

As mentioned above, the thalamus has fallen by the wayside as a target for PDbecause of its limited effects on bradykinesia and rigidity The GPi and STNare clearly the two structures most commonly targeted today for PD, andmost centers are using DBS rather than ablative procedures even though nodouble-blind, randomized, head-to-head comparison has been conductedbetween ablative therapy and DBS

It is unclear whether GPi DBS or STN DBS is superior Burchiel et al.(8) conducted a small randomized prospective trial comparing pallidal tosubthalamic stimulation in 10 patients with advanced PD, and found nosignificant difference in off medication UPDRS motor scores between thetwo groups, although medications were able to be decreased in the STNgroup but not the GPi group This trial was too small, however, to drawany solid conclusions The Deep Brain Stimulation for Parkinson’s DiseaseStudy Group performed a large multicenter trial that enrolled 96 patientswith STN DBS and 38 patients with GPi-DBS (11) Because patients werenot randomized in this trial, it is difficult to compare the two groups, butthe STN group appeared to have more favorable outcomes Another pro-spective nonrandomized study carried out by Krause et al (60) also sug-gested that the STN was the better target for all parkinsonian symptoms,but GPi stimulation was superior for reduction of dyskinesias.

One of the most consistent differences between the two sites is thatSTN stimulation allows patients to reduce dopaminergic medications,whereas daily levodopa equivalent doses in those undergoing pallidal stimu-lation remain largely unchanged Many studies have also noted that STNstimulation requires less electrical energy than GPi-DBS (11,61), whichallows for a longer battery life GPi stimulation, however, does not seem

to be associated as consistently with cognitive and psychiatric side effects

as STN stimulation (51,53,57,59) Clearly, a large randomized comparisonbetween the two targets needs to be completed before recommending oneprocedure over the other The VA and NIH are currently supporting amulticenter trial of DBS in PD to address the comparative efficacy of GPiand STN stimulation

3.1.4 Novel Surgical Strategies

Although DBS and surgical ablation are effective for the symptoms of PD,they may not interfere with the underlying neurodegenerative process andthus do not slow down or reverse the course of the illness Consequently,much research is being conducted to evaluate alternative therapies and stra-tegies that may alter the long-term outcome in these patients One of thesenovel approaches is cell transplantation Thus far, two human clinical trials

of fetal nigral transplantation have been conducted, and although bothstudies showed uptake of the embryonic dopamine neurons in the basalganglia on imaging and post-mortem examinations, both trials failed tomeet statistical significance in their outcome measures (62,63) An unantici-pated finding was the development of disabling off-medication dyskinesias

in some transplanted patients These findings, along with ethical concernsand the scarcity of human fetal tissue, currently limit the usefulness of fetalnigral transplantation as a viable clinical option for patients with PD Othersources of cells for transplantation into patients include xenografts (fromfetal pigs) (64) and embryonic stem cells, though these techniques still need

to be refined and tried in small groups of patients before a large clinical trialcan even be attempted (65).

Another top prospect for therapeutic trials in PD is glial derivedneurotrophic factor (GDNF) GDNF has been extensively studied in animalmodels of PD and promotes dopamine neuron survival and growth (66) Sofar, a few clinical trials with GDNF have been undertaken in patients with

PD In the first trial, conducted by Nutt et al (67), GDNF or placebo wasadministered through an intracerebroventricular catheter in 50 patients withadvanced PD The patients had multiple side effects, including nausea,vomiting, and anorexia, but did not have any improvement in UPDRSscores, likely because the GDNF did not reach the appropriate brainregions Gill et al (68) infused GDNF directly into the putamen of five

PD patients, and reported a 39% improvement in the UPDRS tion motor score and a reduction in dyskinesias by about 64% In addition,fluorodopa scans showed a 28% increase in putamenal uptake However, arecent double-blind trial of intraputaminal GDNF was stopped because asix month analysis indicated no clinical benefit, causing the manufacturer,Amgen, to withdraw GDNF from all clinical trials

off-medica-3.2 Essential Tremor

Tremor is a rhythmic oscillation of a body part that is produced by alternatingcontractions of reciprocally innervated muscles (69) Of all the tremorsyndromes, ET is the most common (70), yet fewer ET patients are referredfor surgery than PD patients One probable reason is that most ET patientssuffer from a mild tremor which is either not severe enough to seek medicaltreatment, or can be controlled with medication (71) However, when tremor

in ET is severe, it can be severely disabling, as well as cause significant socialembarrassment ET generally presents as a bilateral, symmetric posturaland/or kinetic tremor of the hands, but it can commonly affect the head andvoice as well (72) Primidone and propranolol are considered first-line therapyand should be tried alone or in combination before considering surgery (71).The thalamus has been considered the optimal target for tremor eversince Hassler and colleagues reported better tremor control with thalamiclesions over 40 years ago (73,74) However, because of the success of STNstimulation in controlling parkinsonian tremor (8,11,22,23), some groupshave begun to experiment with STN DBS for ET, with promising results

in a small number of patients to date (75–78)

3.2.1 Ablative Procedures: Thalamotomy

Many investigators have reported successful suppression of tremor in ET withthalamotomy (79–86) In the majority of these studies, greater than 90% ofpatients had improvement of tremor in the limb contralateral to the lesion.Moreover, long-term studies indicate sustained benefit (80,81,83) In the

largest long-term series published (81), of 65 patients with ET who were lowed for a mean of 8.6 years, 80% continued to have contralateral tremorimprovement While adverse effects of thalamotomy are usually transient,persistent postoperative complications common to most of these studiesinclude paresthesias, motor weakness, dysarthria, disequilibrium, and gaitdisturbance, occurring in approximately 10–20% of patients (80,81,83) It isimportant to note that almost all of the ET patients underwent unilateralthalamotomy, likely because of the data from the PD literature, whichdemonstrated a high occurrence of speech and cognitive disturbance frombilateral procedures (28,29).

fol-3.2.2 Deep Brain Stimulation

Some ET patients cannot be adequately treated with unilateral thalamotomy,either because of midline tremor, such as head tremor, or severe bilateral handtremors However, due to the adverse effects associated with bilateral thala-motomies mentioned above, DBS of the VIM nucleus of the thalamus hasbecome an increasingly popular surgical option Benabid and colleagues werethe first to report the successful treatment of limb tremor in ET using chronicVIM stimulation in a series of patients (87) Since then, a number of investi-gators have echoed Benabid et al.’s findings of the safety and efficacy of tha-lamic DBS in patients with ET, and many have published long-term results.Koller et al (88) followed 25 patients with ET for a mean of 40 months afterunilateral VIM DBS implantation, and found sustained tremor improvement(50% based on tremor rating scales) with little change in electrical stimulus

parameters over time Similar results were reported by a Swedish group (89)and a multicenter European group (90) for at least 6 years of follow-up In all

of these studies, adverse effects were minimal, and typically could be corrected

by adjusting the stimulator, but required battery replacement every 3–6 years.Thalamic stimulation has also been shown to improve health-related quality

of life for ET patients (91)

Fewer studies have focused on midline tremors, such as head or voicetremor, in patients with ET Carpenter et al (92) studied the effect ofthalamic stimulation on voice tremor in seven patients undergoing DBSfor hand tremor, and noticed mild improvement for four patients Koller

et al (93) evaluated unilateral thalamic DBS in 38 patients with head tremordue to ET At one year post implantation, 75% reported improvement inhead tremor Ondo et al (94) studied 14 ET patients with head tremorand reported a 55% improvement at 3 months with unilateral thalamicstimulation Obwegeser and colleagues found that although unilateral thala-mic DBS resulted in a mild improvement in head tremor, there was an addi-tional effect from bilateral stimulation (95) Furthermore, improvements invoice tremor (83%), tongue tremor (100%), and face tremor (100%) werenoted with bilateral stimulation as well Adverse effects from stimulationincluded dysarthria, disequilibrium, and paresthesias, similar to those

reported in the long-term studies mentioned previously (88–90), but allresolved with stimulator adjustment In the study conducted by Taha

et al (96), 9 of 10 patients with head tremor and 6 of 7 patients with voicetremor undergoing bilateral thalamic stimulation had greater than 50%improvement in tremor

3.2.3 Thalamotomy vs Thalamic DBS

A couple of studies have attempted to address whether thalamic ablative gery or DBS implantation is better for the surgical treatment of ET Tasker

sur-et al (84) rsur-etrospectively compared 19 patients with DBS implants to

26 patients who underwent thalamotomy Although most of the patients had

PD tremor (only three patients in each group were diagnosed with ET), cacy was similar in both groups Thalamotomy had to be repeated in 15% ofpatients, while there were no revisions of DBS implants Pahwa and collea-gues (85) studied 34 ET patients retrospectively, 17 of whom were treatedwith thalamic stimulation, and 17 with thalamotomy Again, there were nodifferences in efficacy, but the thalamotomy group had more surgical compli-cations, including intracranial hemorrhages, cognitive abnormalities, hemipar-esis, and aphasia Finally, Schuurman et al (86) conducted a prospectiverandomized study comparing thalamic DBS to thalamotomy, and concludedthat both techniques were equally effective for tremor suppression, but that sti-mulation resulted in fewer adverse effects with improved function As a result,DBS has virtually replaced thalamotomy for ET However, there may still be arole for thalamotomy, especially if the patient is older or if there are barriersthat prevent the patient from following up consistently postimplantation (97)

effi-3.3 Other Tremor Disorders

Patients with tremors of other etiologies, such as cerebellar tremor due tomultiple sclerosis (MS), posttraumatic tremor, or poststroke tremor tendnot to respond to pharmacologic therapy (98), and may be candidates forstereotactic neurosurgery Thalamic stimulation has been the most commonsurgical approach applied to these disorders, but success has been variable,and consists only of case reports or small case series Among these other tre-mor disorders, cerebellar tremor secondary to MS has been the most studied(47,99–103), and results in general have shown that the postural component

of the tremor in MS improves the most, whereas the action componentresponds variably and the cerebellar dysfunction remains unchanged.Unfortunately, it was impossible to predict which MS patients wouldrespond to stimulation, based on clinical, radiological, or intraoperativegrounds (100,103) Furthermore, those patients who responded to stimu-lation developed a ‘‘tolerance’’ to the treatment, and required frequentstimulator adjustments to maintain limb function (99,101–103) Stimulation

was also less effective for tremor in long-term follow-up, likely due to theprogression of MS (104).

3.4 Dystonia

Dystonia is an abnormal involuntary movement disorder characterized bysustained muscle contractions, which often result in twisting, writhing move-ments, or abnormal posturing (105) Dystonias can be classified by etiology(primary or secondary) or by body region (general, segmental or focal).Primary dystonias may be generalized, focal, or segmental Generalizedprimary dystonia usually starts in childhood and has a genetic etiology(e.g., DYT-1) but may also be idiopathic Focal primary dystonias, such

as cervical dystonia (CD), hemifacial spasm, and blepharospasm, tend

to occur in adulthood and are usually idiopathic The causes of secondarydystonias are varied, and include birth trauma (cerebral palsy), multiplesclerosis, structural lesions (tumor or stroke), drugs (e.g., neuroleptics),metabolic disorders, and neurodegenerative processes such as PD

Botulinum toxin is the preferred treatment for most focal and segmentaldystonias Too many different muscles are involved and too much botulinumtoxin is needed to make this therapy practical for the treatment of generalizeddystonia, for which anticholinergics and muscle relaxants are generally thefirst pharmacological agents prescribed Stereotactic neurosurgery is reservedfor those patients that have failed oral medications and/or botulinum toxintreatments Although both ablative and deep brain stimulation techniqueshave been shown to be of benefit for most dystonias, the results vary widelybetween studies This is likely due to the fact that there is significant clinicalheterogeneity in the dystonia population, making it difficult to draw solidconclusions

3.4.1 Chemodenervation

Botulinum toxin A (BotoxÕ) was first shown to be effective for cervical tonia by Tsui et al in 1986 (106) Since then, Botox has been demonstrated

dys-to have long-term safety and efficacy for focal and segmental dysdys-tonias such

as CD, blepharospasm, and hemifacial spasm (107–109) Botulinum toxin

is a protein produced by the anaerobic bacterium, Clostridium botulinum,and exists as several immunological types, labeled A to G Types A and B(Myobloc) are commercially available in the United States The toxin isinjected directly into the muscle and works by blocking the presynapticrelease of acetylcholine at the neuromuscular junction This results indecreased contraction of the muscle, thus relieving the involuntary move-ments and oftentimes the pain as well

A clinical response from Botox usually occurs within 1 week afterinjection, and usually lasts 3–4 months Common side effects includeinjection site pain, bruising, and focal weakness (107,110) Other side effects

include a flu-like syndrome, and if injected into the neck muscles for CD,dysphagia (110) Some patients (5–10%) may experience diminishing effectfrom repeated treatments; this is often due to the development of antibodies

to botulinum toxin (107,109,111,112)

3.4.2 Ablative Procedures

Early on, thalamotomy seemed to be the preferred procedure for dystonia,largely due to the results published by Cooper from the late 1950s to the1970s (113) He performed thalamotomies on over 200 patients withprimary generalized dystonia, and after an average follow-up of 7.9 years,approximately 70% had mild to marked improvement in their symptoms.Subsequent case series were also positive, although less favorable, withimprovement seen in only 25–60% of all cases (114–117), and no significantoverall difference in response between dystonias of primary or secondaryetiologies Though Cardoso et al (117) noted better results for generalizeddystonia (80% of patients improved) than other subgroups, and Andrew

et al (115) found that hemidystonia patients improved dramatically(100% showing fair to excellent improvement), the overall results of thesestudies suggest that there is no enhanced benefit from thalamotomy forany particular subgroup of dystonia patients Furthermore, thalamotomy

is associated with significant complications, notably dysarthria, especially

if performed bilaterally (56–73% of patients) (115,116)

Pallidotomy was not widely performed for dystonia until studies ofpatients with PD undergoing pallidotomy reported a dramatic reduction

in levodopa induced dyskinesias, both choreic and dystonic, and off-perioddystonia (35,118,119) Seeing these encouraging results, many surgical centersthen tried applying pallidotomy to patients with dystonia, and the GPi is nowconsidered the target of choice for the treatment of dystonia (120) Overall,primary generalized dystonia patients seem to benefit more from pallidotomy(120–126), with mean reductions in the Burke–Marsden–Fahn dystonia ratingscale (127) by 59–80% (122,124–126) Typically, the improvement is mild

to moderate in the immediate postoperative period, but continues to showgradual improvement over the next few months (120–122) Most patients inthe studies cited tolerated pallidotomy well, with minimal complications Inthe study reported by Yoshor et al (120), 6 of 18 patients undergoing thala-motomy had postoperative complications compared to 2 of 14 patients under-going pallidotomy

3.4.3 Deep Brain Stimulation

Though results from thalamic DBS were published as early as the late 1970s(128), most of the literature has focused instead on the globus pallidus as astimulation target, likely because the data from ablative proceduressuggested that GPi was a more effective site, but also because the fewreports of thalamic DBS in dystonia have had generally poor results The

Grenoble group, in reviewing their experience with thalamic stimulation formovement disorders, noted that their five patients with dystonia were

‘‘inconsistently, less significantly, or not improved’’ (129)

Vercueil et al (130) implanted DBS leads into the thalamus of

12 patients, and although six of the patients rated their global functional come as satisfactory, dystonia rating scales and disability scales were notimproved Finally, Kupsch et al (131) reported eight patients with heteroge-neous causes of dystonia who underwent simultaneous bilateral GPi and VIMelectrode implantation, with only two patients benefiting from stimulation ofthe VIM

out-As with pallidotomy, the results from the pallidal DBS literature fordystonia are more encouraging Indeed, in the few series where patientsunderwent both thalamic and GPi stimulation, the latter site seemed toresult in greater improvement (130,131) Pallidal stimulation has beendemonstrated to be effective for both primary (130,132–136) and secondarydystonia (130,134–136) although it appears to be most successful for gener-alized DYT-1 dystonia (132,136,137) The seven DYT-1 dystonia patients(six children, one adult) reported by Coubes et al (132), had a meanimprovement of 90.3% as measured by the Burke–Marsden–Fahn dystoniarating scale This improvement appeared to be sustained after 2 years offollow-up (136) Primary DYT-1 negative dystonias, including idiopathicgeneralized dystonia as well as cervical dystonia, generally see between 20%and 80% improvement in their symptoms (133–136), while those with sec-ondary dystonias, unfortunately, have even more variable results (134–136).This wide range in the amount clinical benefit is likely due to the heterogeneity

of the dystonia population Nevertheless, this provides intractable dystoniapatients, whether primary or secondary, with another treatment option wherebefore there was no palatable alternative In contrast to DBS for PD, theeffects from stimulation in dystonia tend to be more gradual, and the voltagesand pulse widths used tend to be higher (131)

STN DBS is just starting to receive attention as a possible treatmentfor dystonia of either primary or secondary etiologies The first clinicalevidence to support studying the STN as a target for dystonia came fromLimousin et al (55), who found that off-period dystonia in PD patientsdisappeared with high-frequency stimulation of the STN The same investi-gators then placed STN stimulators in four generalized dystonia patients inaddition to 22 patients with PD who exhibited severe off-period dystonia(138) Although off-period dystonia was reduced by 70% in the PD patients,the generalized dystonia patients unfortunately had no benefit This is in con-trast to the case series reported by Sun et al (139), in which four generalizeddystonia patients all improved with STN stimulation, and the cervical dysto-nia patient reported by Chou et al (75), whose pain and dystonic neck pos-ture improved with stimulation of the STN These results are encouraging,

but further investigations are necessary before recommending the mic nucleus as a target for the treatment of dystonia.

subthala-3.4.4 Comparison of Targets and Procedures

As mentioned earlier, most centers for movement disorders appear to betargeting the globus pallidus for dystonia, likely because the results frompallidotomy and pallidal DBS are more dramatic with fewer complications.Yet, there have been no prospective, head-to head trials comparing the glo-bus pallidus to the thalamus, and thus, neither site has been proven to besuperior to the other Further, the STN needs to be further evaluated as apotential target for dystonia surgery The retrospective study by Yoshor

et al (120) comparing thalamotomy versus pallidotomy suggests significantlybetter long-term improvement from pallidotomy, but comparisons betweenthe two groups are limited because some had bilateral surgeries while othershad unilateral Further investigations comparing the two sites need to beperformed in order to determine the optimal site It also remains to be seenwhether or not the subthalamic nucleus plays a role in the treatment ofdystonia Moreover, although the pendulum is swinging towards DBS overablative surgery, no comparative study has been performed between DBSand ablation for dystonia It is essential that such a study be conducted, asses-sing relative efficacy, complications, and cost-effectiveness so that optimalprocedure can be recommended

3.5 Spasticity

Spasticity is defined as an increase in muscle tone that is velocity dependent(140), and when severe, can manifest as painful muscle spasms and impairfunction As with other movement disorders, surgery is indicated for severespasticity only when noninvasive treatment with oral muscle relaxants, benzo-diazepines, and physical therapy has failed Historically, many differentsurgical approaches to spasticity have been attempted, including stereotacticbrain surgery (141), cerebellar stimulation (142), and myelotomy (143) Theseprocedures, however, ultimately proved unsuccessful and no longer play arole in the surgical treatment of spasticity Instead, intrathecal baclofen andselective posterior rhizotomy have emerged as the most commonly recom-mended neurosurgical therapies Intrathecal baclofen, because it is a reversi-ble procedure that has been proven to be effective, is often considered beforeselective posterior rhizotomy, an irreversible neuroablative technique bettersuited for patients with focal spasticity

Baclofen is a gamma-aminobutyric acid (GABA) agonist whose neteffect is to inhibit spinal synaptic reflexes, and intrathecal infusion allowshigher levels of the drug to be delivered in the central nervous system whencompared to oral administration (144) The clinical effectiveness of intrathecalbaclofen was first demonstrated by Penn and Kroin (144,145), and has since

been substantiated by others (140,146–148) Potential candidates for cal baclofen are first given a trial through a percutaneous catheter or accessport If candidates respond, an electronic pump is then implanted subcuta-neously Hardware complications often occur, including catheter occlusion,migration, disconnection, or infection (140,146) Baclofen itself is a centralnervous system depressant, and can cause sedation and drowsiness, and inhigh doses can induce respiratory depression and coma (148).

intrathe-Dorsal rhizotomy is one of the oldest surgical procedures for city, but the technique has been refined over the years to what is now known

spasti-as selective posterior rhizotomy (SPR) This procedure relieves spspasti-asticity byinterrupting the peripheral stretch reflex, and can be performed in thecervical or lumbar areas In the peripheral stretch reflex arc, impulses frommuscle spindle fibers detecting a passive stretch are delivered through theposterior nerve roots and synapse on the alpha motor neuron, which thenfires to contract the stretched muscle In SPR, usually one quarter to onehalf of these posterior nerve roots are severed SPR has been evaluated inthree different prospective randomized trials for spasticity in cerebral palsy(149–151) A meta-analysis of these three trials concluded that SPR, alongwith physical therapy, reduces spasticity in children with cerebral palsy(152) Side effects of the procedure include sensory loss, weakness, andbowel or bladder dysfunction

4 CONCLUSIONS

Functional neurosurgery for movement disorders has evolved considerably

in recent years Many patients with a variety of symptoms enjoy significantlyimproved quality of life with minimal side effects There are now more treat-ment options for patients suffering with advanced PD, ET, cerebellar tre-mor, dystonia, and spasticity, and even more promising therapies are onthe horizon Nevertheless, surgical therapies for movement disorders as awhole still do not yet meet evidence-based standards Further studies areessential in order to clarify the surgical targets and techniques that are opti-mally suited to treat patients with each of these devastating conditions

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